title: Sugammadex is cleared rapidly and primarily unchanged via renal excretion.
abstract: Sugammadex is a modified γ-cyclodextrin which rapidly reverses rocuronium-and vecuronium-induced neuromuscular blockade. Previous studies suggest that sugammadex is mostly excreted unchanged via the kidneys. This single-center, open-label, non-randomized study used (14)C-labeled sugammadex to further investigate the excretion, metabolic and pharmacokinetic (PK) profiles of sugammadex in six healthy male volunteers. (14)C-labeled sugammadex 4 mg/kg (0.025 MBq/kg of (14)C-radioactivity) was administered as a single intravenous bolus. Blood, urine, feces and exhaled air samples were collected at pre-defined intervals for assessment of sugammadex by liquid chromatography-mass spectrometry (LC-MS) and for radioactivity measurements. Adverse events were also assessed. Excretion of sugammadex was rapid with ∼70% of the dose excreted within 6 h and ∼90% within 24 h. Less than 0.02% of radioactivity was excreted in feces or exhaled air. Ninety-five percent of the radioactivity detected in urine could be attributed to sugammadex, as determined by LC-MS, suggesting very limited metabolism of sugammadex. LC-MS analysis of plasma samples found that sugammadex accounted for 100% of total (14)C-radioactivity in the plasma. In general, PK parameters determined from radioactivity and sugammadex plasma concentrations were very similar. Any adverse events were of mild-to-moderate intensity, and judged unrelated to sugammadex. These findings demonstrate that sugammadex is cleared rapidly, almost exclusively via the kidney, with minimal or no metabolism.
authors.affiliation: MSD, Oss, The Netherlands. pierre.peeters2@merck.com
authors.forename: Pierre
authors.initials: P
authors.lastname: Peeters
authors.forename: Paul
authors.initials: P
authors.lastname: Passier
authors.forename: Jean
authors.initials: J
authors.lastname: Smeets
authors.forename: Alex
authors.initials: A
authors.lastname: Zwiers
authors.forename: Marcel
authors.initials: M
authors.lastname: de Zwart
authors.forename: Saskia
authors.initials: S
authors.lastname: van de Wetering-Krebbers
authors.forename: Marlou
authors.initials: M
authors.lastname: van Iersel
authors.forename: Sjoerd
authors.initials: S
authors.lastname: van Marle
authors.forename: Diels
authors.initials: D
authors.lastname: van den Dobbelsteen
mesh_terms: D000328:Adult; D000368:Aged; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors*; D000077122:Sugammadex; D047408:gamma-Cyclodextrins / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D003473:Neuromuscular Nondepolarizing Agents; D047408:gamma-Cyclodextrins; D000077122:Sugammadex